The effects of magainin 2-derived and rationally designed antimicrobial peptides on Mycoplasma pneumoniae

Abstract

Combating the spread of antimicrobial resistance (AMR) among bacteria requires a new class of antimicrobials, which desirably have a narrow spectrum because of their low propensity for the spread of AMR. Antimicrobial peptides (AMPs), which target the bacterial cell membrane, are promising seeds for novel antimicrobials because the cell membrane is essential for all cells. Previously, we reported the antimicrobial and haemolytic effects of a natural AMP, magainin 2 (Mag2), isolated from the skin of Xenopus laevis (the African clawed frog), four types of synthesised Mag2 derivatives, and three types of rationally designed AMPs on gram-positive and gram-negative bacteria. To identify novel antimicrobial seeds, we evaluated the effect of AMPs on Mycoplasma pneumoniae, which also exhibits AMR. We also evaluated the antimicrobial effects of an AMP, NK2A, which has been reported to have antimicrobial effects on Mycoplasma bovis, in addition to Mag2 and previously synthesised seven AMPs, on four strains of M. pneumoniae using colorimetric, biofilm, and killing assays. We found that three synthesised AMPs, namely 17base-Ac6c, 17base-Hybrid, and Block, had anti-M. pneumoniae (anti-Mp) effect at 8–30 μM, whereas others, including NK2A, did not have any such effect. For the further analysis, the membrane disruption activities of AMPs were measured by propidium iodide (PI) uptake assays, which suggested the direct interaction of AMPs to the cell membrane basically following the colorimetric, biofilm, and killing assay results. PI uptake assay, however, also showed the NK2A strong interaction to cell membrane, indicating unknown anti-Mp determinant factors related to the peptide sequences. Finally, we conclude that anti-Mp effect was not simply determined by the membrane disruption activities of AMPs, but also that the sequence of AMPs were important for killing of M. pneumoniae. These findings would be helpful for the development of AMPs for M. pneumoniae.

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

“…Hiyash et al investigated a variety of natural and synthetic AMPs including Mag2, NK2A, and seven synthesized Mag2-derived AMPs (Mag2-17base, 17base-Aib, 17base-Ac6c, 17base-Hybrid, Block, Stripe, and Random). Three synthesized AMPs, i.e., 17base-Ac6c, 17base-Hybrid, and Block, had activity against Mycoplasma pneumoniae [92]. The screening of derivatives from the AMP D51 against Bacillus cereus (a food poisoning bacterium) highlighted the peptides D51-P11G and D51-P11K for their anti-spore germination and anti-biofilm activities, which they instigated via membrane lysis [93].…”

Antimicrobial Profile from Frog Skin Peptides

“…This mechanism differs from traditional antibiotics, which often target specific bacterial processes, thereby reducing the likelihood of resistance development. Given their unique mode of action and broad-spectrum activity, AMPs such as Magainin 1 3 , Magainin 2 13,14 , and Bombesin 15 hold promise as alternative or adjunctive therapies to combat antibiotic-resistant infections.…”